NM_001103.4(ACTN2):c.343G>A (p.Val115Met) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 24, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000806976.5

Allele description [Variation Report for NM_001103.4(ACTN2):c.343G>A (p.Val115Met)]

NM_001103.4(ACTN2):c.343G>A (p.Val115Met)

Gene:

ACTN2:actinin alpha 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_001103.4(ACTN2):c.343G>A (p.Val115Met)

HGVS:

NC_000001.11:g.236718995G>A
NG_009081.2:g.59855G>A
NM_001103.4:c.343G>AMANE SELECT
NM_001278343.2:c.343G>A
NM_001278344.2:c.-479G>A
NP_001094.1:p.Val115Met
NP_001094.1:p.Val115Met
NP_001265272.1:p.Val115Met
LRG_436t1:c.343G>A
LRG_436:g.59855G>A
LRG_436p1:p.Val115Met
NC_000001.10:g.236882295G>A
NG_009081.1:g.37526G>A
NM_001103.2:c.343G>A
NM_001103.3:c.343G>A
c.343G>A

Protein change:

V115M

Links:

dbSNP: rs397516579

NCBI 1000 Genomes Browser:

rs397516579

Molecular consequence:

NM_001278344.2:c.-479G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001103.4:c.343G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001278343.2:c.343G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1AA (CMD1AA)
Synonyms:: CARDIOMYOPATHY, DILATED, 1AA, WITH OR WITHOUT LEFT VENTRICULAR NONCOMPACTION; CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 23, WITH OR WITHOUT LEFT VENTRICULAR NONCOMPACTION
Identifiers:: MONDO: MONDO:0012808; MedGen: C2677338; Orphanet: 154; OMIM: 612158

Name:: Primary familial hypertrophic cardiomyopathy (HCM)
Synonyms:: Hereditary ventricular hypertrophy; Idiopathic hypertrophic subaortic stenosis
Identifiers:: MONDO: MONDO:0024573; MeSH: D024741; MedGen: C0949658; OMIM: PS192600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000947000	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 24, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20474083, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000947000

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 24, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A novel custom resequencing array for dilated cardiomyopathy.

Zimmerman RS, Cox S, Lakdawala NK, Cirino A, Mancini-DiNardo D, Clark E, Leon A, Duffy E, White E, Baxter S, Alaamery M, Farwell L, Weiss S, Seidman CE, Seidman JG, Ho CY, Rehm HL, Funke BH.

Genet Med. 2010 May;12(5):268-78. doi: 10.1097/GIM.0b013e3181d6f7c0.

PubMed [citation]

PMID:: 20474083
PMCID:: PMC3018746

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000947000.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 43936). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 20474083). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 115 of the ACTN2 protein (p.Val115Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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